The long-term objective of the proposed research is to understand the mechanisms of action of antiarrhythmic drugs on ionic channels in cardiac cells. The specific aim of these studies is to determine the modes of action of a number of antiarrhythmic drugs on ionic channels in developing heart. The drugs include Dilantin, lidocaine, digoxin and amiodarone. The experiments are designed to study the effects of these drugs on ionic channels in different ages of cultured cardiac cells using voltage clamp and patch clamp techniques. The objectives of these experiments are (a) to determine the properties of ionic channels in fetal and neonatal ventricular myocytes, (b) to characterize the actions of these drugs on ionic channels in cardiac cells which undergo developmental changes, and (c) to study the effects of lidocaine and Dilantin on digoxin or toxin-treated cardiac cells. The ionic current will be measured in different ages of cultured rat aggregate under voltage clamp conditions. Patch pipette voltage clamp technique will be used. The fundamental knowledge obtained from these experiments will be essential in defining the mechanisms of action of antiarrhythmic agents in developing heart.